Phenotypic Diversity of Cryptococcus neoformans var. neoformans Clinical Isolates from Localized and Disseminated Infections.

Zena M Birkenfeld,Albrecht F Kiderlen,Thomas Harrer,Nikita Dittel,Christoph Stephan,Volker Rickerts

doi:10.3390/microorganisms10020321

Abstract

Cryptococcus neoformans var. neoformans is the second most prevalent agent of cryptococcosis in central Europe. Infections mostly present with localized skin and disseminated infections. Previous studies did not find these presentations to be determined by the fungal genotype as detected by multilocus sequence typing (MLST). However, phenotypic fungal traits may impact clinical presentation. Here, we studied the growth and virulence factors of C. neoformans var. neoformans isolates from disseminated and localized infections and an environmental isolate. We used coincubation with Acanthamoeba castellanii and the Galleria mellonella infection model to identify phenotypic characteristics potentially associated with clinical presentation. Clinical isolates of C. neoformans var. neoformans present a substantial phenotypic variability. Median survival of G. mellonella varied between 6 and 14 days. C. neoformans var. neoformans isolates from disseminated infections showed stronger melanization and larger capsules. They demonstrated superior uptake into an amoeba and increased cytotoxicity for the amoeba. Differences of strains from localized and disseminated infections in coincubation with amoeba are in line with the importance of phagocytes in the pathogenesis of disseminated cryptococcosis. Phenotypic traits and non-vertebrate infection models may help understand the virulence potential of C. neoformans var. neoformans isolates.

Highlights

Infection models generally suggest a lower virulence of C. neoformans var. neoformans strains as compared to C. neoformans var. grubii [7]
We studied C. neoformans var. neoformans isolates from patients with either disseminated or localized skin infections diagnosed in Germany and an environmental isolate from Germany to compare virulence factors and fungus–host interaction in two alternative host models to document phenotypic diversity of these fungi and screen for factors associated with different clinical presentations
This report documents substantial phenotypic variability of C. neoformans var. neoformans isolated in Germany

Summary

Introduction

Phenotypic fungal traits may impact clinical presentation. We used coincubation with Acanthamoeba castellanii and the Galleria mellonella infection model to identify phenotypic characteristics potentially associated with clinical presentation. Neoformans isolates from disseminated infections showed stronger melanization and larger capsules. They demonstrated superior uptake into an amoeba and increased cytotoxicity for the amoeba. Phenotypic traits and non-vertebrate infection models may help understand the virulence potential of C. neoformans var. Infection models generally suggest a lower virulence of C. neoformans var. These infections may present with diverse clinical syndromes including primary cutaneous cryptococcosis, often in non-immunocompromised hosts [8]

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Discussion

Conclusion